Summary of Work: Age at menopause has been proposed as a marker of aging and health. In an analysis of data from the National Health and Examination Survey (NHANES) Epidemiologic Follow-up Study; 2,562 women ages 50 to 86 were included, 299 deaths occurred over a mean follow-up time of 4.0 years. Compared with women who were menstruating at least to age 50, the adjusted rate ratio (RR) was 1.51 (95% confidence interval, CI, (0.97-2.35)) for women with a natural menopause at age < 40, 1.06 (95% CI (0.73-1.53)) for menopause ages 40-44, and 0.96 (95% CI (0.72-1.26) for menopause ages 45-49. The NHANES-III study, conducted from 1988-1994 provides another opportunity to examine specific medical and behavioral risk factors for early menopause. We are conducting a nested case-control analysis using these data; "cases" are selected from women currently age 35 - 49 years who reported a natural menopause at ages 30-46; controls are selected from the remaining women, frequency matched (5 controls:1 case) to the distribution of current age of the case group. The risk factors we will examine include smoking history (personal and passive), body mass, and diabetes. We are also examining correlates with early follicular phase FSH and LH, measured in pre-menstruating women, in a separate analysis of the NHANES-III data. We are also developing a population-based case-control study of early ovarian failure as an add-on to the Agricultural Health Study to address specific hypotheses concerning familial and environmental risk factors, including environmental tobacco smoke, galactose consumption and metabolism, and organochlorine pesticide exposure. We will also examine menstrual, reproductive, and medical history, particularly with respect to autoimmune diseases, as risk factors for early ovarian failure.